The goal of this project is to study the host response to onchocercal infection in order to understand the pathogenesis of clinical disease, the immune mechanisms important in the persistence of the parasite within the host and in protective immunity, and to develop improved immunodiagnostic techniques. The initial phase has involved detailed clinical and laboratory assessment of the severe side effects (Mazzotti reaction) that accompany treatment of the infection and limit the potential of mass chemotherapy for onchocerciasis. Twenty-four patients were treated at a research center in Ghana and subjected to intensive immunologic and clinical evaluation during their Mazzotti reactions. Hypotension, fever, adenitis and puritis all were correlated with infection intensity after detailed statistical analyses were carried out. Most prominent of the immunological changes was a dramatic fall of serum complement levels within 2 hours of initiating treatment and evidence for activation of immediate hypersensitivity immune mechanisms, the latter including evidence of eosinophil and mast cell degranulation both morphologic around microfilariae being killed in the skin and biochemical with rises in serum eosinophil granule protein concentrations. Specific IgE antibodies (assessed by histamine release and radioimmunoassay) and extremely high levels of total IgE were demonstrated pre-treatment and likely were important in mast cell degranulation after antigen was released from dying pa6asites. Thus, immediate hypersensitivity immune mechanisms, whether triggered by complement-derived anaphylotoxin, specific IgE antibody or eosinophil-derived proteins appear as important determinants of the Mazzotti reaction in man. Also in progress is a study of the immunopathology of onchocercal eye lesions using ocular tissue and fluids removed from patients with onchocerciasis at the time of cataract surgery carried out in Ghana.